Database of genomic biomarkers for cancer drugs and clinical targetability in solid tumors.
Database of genomic biomarkers for cancer drugs and clinical targetability in solid tumors.
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DOI：
10.1158/2159-8290.cd-14-1118
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发表时间：
2015-02
期刊：
影响因子：
28.2
通讯作者：
Guinney J
中科院分区：
文献类型：
--
作者：
Dienstmann R;Jang IS;Bot B;Friend S;Guinney J
全面的基因组图谱有望为癌症治疗带来革命性的变化。在这一前景中，我们提出了突变和拷贝数改变的流行率与不同水平的基因-药物靶向性的实体肿瘤之间的预测性关联。超过90%的TCGA样本具有潜在的靶向改变，其中大多数具有多个事件，说明鉴于基因组环境的复杂性，治疗优先顺序的挑战。在罕见突变的癌基因中，近80%的变异具有不确定的功能意义，反映出我们对许多潜在与治疗行为相关的改变的理解存在差距。在早期临床试验中，靶向药物的使用可能会影响75%癌症患者的治疗决策。大规模分子图谱的预期实施和预测生物标记物的标准化报告是使精确癌症医学成为现实的基本步骤。
Comprehensive genomic profiling is expected to revolutionize cancer therapy. In this Prospective, we present the prevalence of mutations and copy number alterations with predictive associations across solid tumors at different levels of stringency for gene-drug targetability. More than 90% of TCGA samples have potentially targetable alterations, the majority with multiple events, illustrating the challenges for treatment prioritization given the complexity of the genomic landscape. Nearly 80% of the variants in rarely mutated oncogenes are of uncertain functional significance, reflecting the gap in our understanding of the relevance of many alterations potentially linked to therapeutic actions. Access to targeted agents in early clinical trials could affect treatment decision in 75% of cancer patients. Prospective implementation of large-scale molecular profiling and standardized reports of predictive biomarkers are fundamental steps for making precision cancer medicine a reality.